There appear to be a variety of factors involved in genesis, development and maintenance of the hypertensive state. A number of studies implicate alterations of the active component (histamine) in the reduced magnitude of reflex vasodilatation in the hypertensive state in experimental animals. The objective of this study is to evaluate vascular histamine disposition in the spontaneously hypertensive rat. The specific aims are to: 1) characterize the reduction in vascular histamine in the hypertensive state; 2) to determine when in the hypertensive state the defect in histamine disposition occurs; and 3) determine if treatment with an antihypertensive drug can restore the histamine defect. Histamine stored in vasculature is released by sympathetic nerve impulses during activation of the baroreceptor reflex and is thought to contribute to control of vascular resistance to blood flow. More importantly, vascular histamine levels have been shown to be reduced in different models of hypertensive rats in our laboratory. This reduction probably contributes to increases vascular resistance and, thus, to the elevated systemic blood pressure in the hypertensive state. Studies are designed to characterize the reduced histamine content in model vessels (abdominal aorta, femoral, mesenteric) by examining aspects of vascular histamine disposition. Studies include in vitro estimation of histamine synthesis from histidine as well as in vitro determinations of 14C-histidine, 14C-histamine uptake and 14C-histamine release. The catabolism of 14C-histamine in vitro and turnover rates following intravenous 3H-histamine administration will be evaluated in the hypertensive state. Using reserpine and aminoguanidine, the effect of lowering blood pressure or reducing histamine catabolism on restoring vascular content of histamine will be examined. Studies are designed to determine if the histamine defect occurs in the initiation, development of maintenance or the hypertensive state. These data will substantially enhance our progress toward our long term goals of evaluating mechanisms involved in elevated peripheral resistance in hypertension.